Friday, September 7, 2012

Postsurgical Opioid Use – Going Beyond Pain?

OpioidsNewly reported research reveals that in some patients continued opioid analgesic use after surgery has relatively little to do with the actual pain. Psychological distress and potential for substance abuse may be important considerations that practitioners should take into account as risk factors. However, this was a preliminary investigation and the actual message of the study may not be what the researchers intended.

Writing in the in the September issue of Anesthesia & Analgesia, Ian Carroll, MD, from Stanford University, and coauthors note, “previous studies of postoperative opioid use have not reported how substance abuse history and psychological state, rather than injury and pain, might predict a patient’s ongoing choice to stop rather than continue opioid therapy” [Carroll et al. 2012]. Therefore, they designed a study to test the hypothesis that potential substance abuse and psychological distress (anxiety, depression, and posttraumatic stress disorder) are associated with prolonged opioid analgesic use after surgery.

Between January 2007 and April 2009, their prospective, longitudinal inception cohort study enrolled 109 patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. Before surgery, at baseline, a battery of assessment questionnaires measured psychological distress, pain, opioid analgesic use, and risk of developing problematic substance use. Postsurgically the researchers tracked daily use of opioid analgesics until patients reported the cessation of both opioid consumption and pain. The primary end point of interest was time to opioid cessation.

The researchers found that, overall, about 6% of patients were still taking opioids 150 days after their surgeries. Those most likely to be in this group of longer-term opioid users had 3 prior risk factors that were statistically significant:

  • Prior to surgery, 20% of all patients reported taking legitimately prescribed opioids, and these persons were 73% more likely to still be using them longer term after surgery (Hazard Ratio for cessation=0.27; 95% Confidence Interval, 0.13-0.59; P=0.0009).

  • Patients who had self-rated themselves at higher risk of becoming addicted to their opioid medications were 53% more likely to use opioids longer term (HR=0.47; 95% CI, 0.29-0.77; P=0.003).

  • Patients with symptoms of depression at baseline had a 38% higher risk of longer-term opioid analgesic use (HR=0.62; 95% CI, 0.46-0.83; P=0.002. Note: HR data are from Table 3 in the article; however, the increased risk was stated as 42% [HR 0.58], rather than 38%, in the article text and abstract).

Pain duration was significantly correlated with time to opioid cessation with a Pearson correlation coefficient of 0.69 (95% CI, 0.55– 0.78; P<0.0001); however, this accounted for less than half (48%) of the variance — meaning that the 3 factors noted above were at least equally as important as pain duration. Along with that, neither preoperative pain intensity nor the pain intensity at the time of opioid cessation significantly predicted the decision to continue or discontinue opioid analgesics.

The authors conclude that preoperative prescribed opioid use, self-perceived risk of addiction, and depressive symptoms independently and significantly predict more prolonged use of opioids after surgery. This occurred regardless of the type of surgery, and each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity. They recommend that more studies need to be conducted in order to clarify the relationship between opioid abuse and addiction and the 3 major influential factors found in this study.

COMMENTARY: An Unintended Message

This was an interesting study with an important message, but not one that the authors intended. The actual message of this research may be that prescribers are usually very good at starting patients on opioid medications for pain relief, but they are not so good at guiding and supporting those patients in a helpful and timely manner when it comes to discontinuing the analgesics and/or switching to alternative approaches for pain relief.

Instead, the researchers appear to be placing the burden on patients. They observe that, as patients recover from surgery, they have a choice at some point of continuing their prescribed opioids, switching to nonopioid pain management, or discontinuing analgesics. The authors propose that it is not clear at what point prolonged opioid use becomes “chronic” use; however, applying the 6% continuation rate of their study to the nearly 18 million persons undergoing surgical procedures each year, they observe that there would be more than 1 million new long-term users of opioid analgesics each year in the United States alone.

This could be favorable if it meant that previously undertreated patients were receiving better care for pain. Unfortunately, however, it would not be surprising if this research becomes cited as evidence in future editorials or articles advocating against the use of perioperative opioid analgesics whenever possible; arguing that once patients are started on these drugs many of them will find it difficult to stop taking opioids and will become chronic users and potential abusers of the medications.

Already, at least one news report [here] misconstrued the study by featuring the headline “Depression and Painkiller Use Increases Risk of Addiction after Surgery.” It goes on to state, “The risk of addiction to opioid painkillers after surgery significantly increases if a patient is depressed or has used pain medications prior to surgery.” This is not what the study found or the authors intended — addiction per se was not even assessed.

The confusion may be understandable, since there are a number of limitations and mixed messages in this research that should be considered. For one thing, the relatively small numbers of participants in the 5 subgroups, ranging from 12 to 27 subjects, were unlikely adequate to corroborate the statistically significant outcomes reported. The authors do not report having conducted a statistical power analysis to determine if the groups were sufficiently large; rather, they label the research as a “pilot cohort study.”

The authors also do not report on the types of opioids or their dosages, pre- or postsurgery, nor the extent to which this was adequate analgesia. Furthermore, as an observational study, cause-effect relationships cannot be determined and there could be reasons other than those proposed by the authors for opioid continuation after surgery. Here are some considerations — looking at each of the 3 factors the researchers found to be important predictors of prolonged opioid use:

1. Preoperative Opioid Use Predicts Postoperative Continuation?

A considerable number of patients (20%) had been taking prescribed opioid analgesics prior to surgery; although, details regarding the reasons, specific agents, doses, or duration were not reported. And, these patients were more likely to continue taking opioids for longer periods postsurgery.

Furthermore, all study participants had been provided the following directions:

“Following your surgery you are going to have a certain amount of pain for a short period of time. Your doctor will either prescribe pain medication or instruct you to take over-the-counter pain medication. You should take these pain medications only when you are in pain. You should stop taking the medications when you no longer have pain. If you do not require the entire amount of medication prescribed, you should dispose of the remainder. It is alright for you not to finish all the medication you are given.”

Notice that the directions provide no guidance on what to expect when discontinuing opioid medications or how to cope with any unpleasant effects. In a recent UPDATE article [here] we discussed the nuances of naturally occurring physiological dependence and the elusive qualities of true addiction in persons prescribed opioid analgesics. Specifically, we noted that this dependence can begin to develop within only several days of continuous opioid use and discontinuation can incur unpleasant withdrawal symptoms.

When discontinuing opioids, patients may experience such withdrawal symptoms as anxiety, insomnia, increased pain sensation (hyperalgesia), and mood disturbances (anhedonia). In particular, hyperalgesia and anhedonia may explain a worsening of pain and mood that patients may feel as they attempt to self-taper or, worse, abruptly discontinue their analgesics.

Therefore, it makes sense that, as probably occurred in this study, patients with preexisting physiologic dependence on opioids would experience some difficulty in discontinuing those medications after surgery — especially, without supportive guidance from their healthcare providers. In many cases, patients probably confused withdrawal hyperalgesia with unresolved postsurgical pain and the need to continue their medication. In this regard, they were adhering to the directions that they had been given.

2. Depressive Symptoms Affect Continued Opioid Use?

In this study, patients with even minor levels of preoperative depressive symptoms, as measured by scores on the Beck Depression Inventory-II, were more likely to exhibit prolonged use of postsurgical opioids. As noted above, however, anhedonia (mood disturbance and inability to feel pleasure) can be a natural phenomenon of opioid withdrawal.

Therefore, it seems plausible that patients with preoperative depressive symptoms might experience exacerbations of those mood discomforts and have greater difficulty when attempting to discontinue their opioid medications. Of course, this obstacle might be overcome by various types of healthcare provider counseling and support offered to patients, but this was not part of the research design.

3. Self-Perceived Risk of Addiction Prolongs Opioid Use?

AddictionSubjects reporting an increased sense of vulnerability to opioid addiction at baseline continued to take postoperative opioid analgesics significantly longer than patients who did not consider themselves to be at such risk. However, this inference of addiction is probably the most inaccurate and misleading aspect of this study.

As we noted in our earlier UPDATE on this subject, mentioned above, opioid addiction is a complex and multifaceted disease that has eluded adequate definition and measurement in persons with pain receiving opioid analgesic therapy. And, the “Self-Perceived Susceptibility to Addiction” assessment used in this present study was most certainly inadequate.

For this assessment — developed by the researchers themselves — subjects were asked a single question: “How likely do you think it is that you will develop an addiction problem from pain medication you take after surgery?” Patients chose from: “not at all”; “unlikely”; “somewhat likely”; or, “very likely.”

This measure had not been validated as accurate or reliable and the researchers concede that patients do not typically understand distinctions between physical tolerance, substance abuse, and addiction. So, what the patients had in mind when making their self-assessments is completely unknown.

Furthermore, it is of some import that traditionally recognized risk factors for addiction — eg, family history of substance use disorder, personal history of substance abuse, and tobacco or alcohol use — did not predict prolonged continuation of postoperative opioid use in this study. Also, in multivariate analyses, highly validated measures of addiction risk administered to patients at baseline — SOAPP-24 (Screener and Opioid Assessment for Patients with Pain) and the drug and alcohol use section of the Addiction Severity Index (ASI) — were not significantly predictive of continued opioid use.

Of some concern, patients prescribed opioids before surgery were about 5 times more likely to also use illicit opioids than subjects not taking Rx opioids presurgically (Relative Risk=5.2; 95% CI 2.0-13.4; P=0.001). Specifically, 38% of patients taking prescribed opioids and 7% of those not taking opioid medications presurgically self-reported taking illicit opioids; although, the authors do not report the frequency of this misuse, the source of the opioid, or motivation (eg, pain relief vs recreational use) and they did not conduct confirming urine drug tests on the subjects.

However, it is important that in multivariate analyses only preoperative use of legitimately prescribed opioids was a strong predictor of prolonged opioid analgesic use postsurgically. This reinforces the notion, as suggested above, that preexisting physiological opioid dependence — rather than the source of the opioid or opioid misuse — played a most significant role in prolonged use of analgesics.

Doing the “Right Thing”

Perhaps the most remarkable feature of this study is that merely 6% of patients continued to take opioids for 5 months after surgery, but the median time across all 5 groups was only about 26 days. For example, median days to opioid cessation in the total knee replacement group was 47 days, whereas it was only 1 day for lumpectomy. Most importantly, as the authors note, “No patients reported taking opioid medication after pain had resolved and most postsurgical patients stopped opioid use before their pain resolved.”

So, cessation of opioid use was a matter of HOW SOON rather than IF AT ALL (ie, becoming a chronic user), and a great many patients apparently discontinued in the presence of pain and emotional distress that actually might have been due to or exacerbated by opioid withdrawal symptoms. This is despite the fact that the patients received no special guidance for weaning themselves from the analgesics or outside support, including symptom-relieving medications or counseling.

Perhaps a most telling conclusion offered by the authors is the suggestion that patients who are concerned about the risk of becoming addicted to their postsurgical pain medications “may benefit from a more specific, physician-guided opioid taper, rather than being left to titrate off opioids on their own.” Indeed, for all patients — with acute or chronic pain — it may be time for healthcare professional to devote as much attention to safe and comfortable protocols for discontinuing opioid medications, if appropriate or necessary, as they do to safely starting those analgesics in the first place.

There also is the nagging question of how patients can self-manage opioid tapering if they are running out of opioid medication and cannot access more of it. This had been highlighted as a serious problem during past natural disasters, like after hurricane Katrina devastated large portions of southern United States some years ago and many patients were cut off from access to medical care.

In regard to the above concerns, there are two resources from Pain Treatment Topics that may be some help:

  • Opioid Tapering: Safely Discontinuing Opioid Analgesics by Lee A. Kral, PharmD, BCPS [access here].

  • Opioid Tapering During Emergencies; Advice for Patients at Opioids911-Safety [here].

REFERENCE: Carroll I, Barelka P, Wang CKM, et al. A Pilot Cohort Study of the Determinants of Longitudinal Opioid Use After Surgery. Anesth Analgesia. 2012 (Sept);115(3):694-702 [abstract here].

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